Rapid discovery of a novel"green"and natural GST inhibitor for sensitizing hepatocellular carcinoma to Cisplatin by visual screening strategyOA
Rapid discovery of a novel"green"and natural GST inhibitor for sensitizing hepatocellular carcinoma to Cisplatin by visual screening strategy
Over-expression of glutathione S-transferase(GST)can promote Cisplatin resistance in hepatocellular carcinoma(HCC)treatment.Hence,inhibiting GST is an attractive strategy to improve Cisplatin sensi-tivity in HCC therapy.Although several synthesized GST inhibitors have been developed,the side effects and narrow spectrum for anticancer seriously limit their clinical application.Considering the abundance of natural compounds with anticancer activity,this study developed a rapid fluorescence technique to screen"green"natural GST inhibitors with high specificity.The fluorescence assay demonstrated that schisanlactone B(hereafter abbreviated as C1)isolated from Xue tong significantly down-regulated GST levels in Cisplatin-resistant HCC cells in vitro and in vivo.Importantly,C1 can selectively kill HCC cells from normal liver cells,effectively improving the therapeutic effect of Cisplatin on HCC mice by down-regulating GST expression.Considering the high GST levels in HCC patients,this compound demon-strated the high potential for sensitizing HCC therapy in clinical practice by down-regulating GST levels.
Linxi Mao;Wei Wang;Yan Qin;Jialong Fan;Wei Yang;Bin Li;Liang Cao;Liqin Yuan;Mengyun Wang;Bin Liu
TCM and Ethnomedicine Innovation & Development International Laboratory,School of Pharmacy,Hunan University of Chinese Medicine,Changsha,410208,ChinaTCM and Ethnomedicine Innovation & Development International Laboratory,School of Pharmacy,Hunan University of Chinese Medicine,Changsha,410208,China||College of Biology,Hunan University,Changsha,410082,ChinaCollege of Biology,Hunan University,Changsha,410082,ChinaCollege of Foreign Languages,Hunan Women's University,Changsha,410004,ChinaDepartment of General Surgery,The Second Xiangya Hospital,Central South University,Changsha,410011,China
GSTDrug resistanceFluorescenceHepatocarcinomaNatural compound C1"Green"GST inhibitor
《药物分析学报（英文）》 2024 (005)
693-706 / 14
This work was supported by the National Natural Science Foundation of China(Grant Nos.:82003931,82204766 and 81374062),the Outstanding Youth Foundation of Hunan Provincial Education Department of China(Grant No.:20B445),the Hunan Youth Science and Technology Innovation Talents Project,China(Grant No.:2021RC3100),the Chinese Postdoctoral Science foun-dation(Grant No.:2021M690974),Changjiang Scholars Program in Ministry Education,People's Republic of China(Program No.:T2019133),and the Scientific Research Project of Hunan Provincial Education Department(Project No.:21B0394).
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